Article

Meta-analysis of genetic association studies on bipolar disorder

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.27). 07/2012; 159B(5):508-18. DOI: 10.1002/ajmg.b.32057
Source: PubMed

ABSTRACT Numerous candidate gene association studies of bipolar disorder (BP) have been carried out, but the results have been inconsistent. Individual studies are typically underpowered to detect associations with genes of small effect sizes. We conducted a meta-analysis of published candidate gene studies to evaluate the cumulative evidence. We systematically searched for all published candidate gene association studies of BP. We then carried out a random-effects meta-analysis on all polymorphisms that were reported on by three or more case-control studies. The results from meta-analyses of these genes were compared with the findings from a recent mega-analysis of eleven genome-wide association studies (GWAS) in BP performed by the Psychiatric GWAS Consortium (PGC). A total of 487 articles were included in our review. Among these, 33 polymorphisms in 18 genes were reported on by three or more case-control studies and included in the random-effects meta-analysis. Polymorphisms in BDNF, DRD4, DAOA, and TPH1, were found to be nominally significant with a P-value < 0.05. However, none of the findings were significant after correction for multiple testing. Moreover, none of these polymorphisms were nominally significant in the PGC-BP GWAS. A number of plausible candidate genes have been previously associated with BP. However, the lack of robust findings in our review of these candidate genes highlights the need for more atheoretical approaches to study the genetics of BP afforded by GWAS. The results of this meta-analysis and from other on-going genomic experiments in BP are available online at Metamoodics (http://metamoodics.igm.jhmi.edu).

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    • "Owing to the significant diversity in etiology and clinical presentation of bipolar disorder, investigators have sought to define more homogenous subgroups with the goal of identifying genetic biomarkers, further understanding the neurobiology, and delineating more specifically tailored, and thus more efficacious, treatment regimens (Teixeira et al. 2013; Seifuddin et al. 2012; Geoffroy et al. 2013). "
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    • "Please cite this article in press as: Gatt JM, et al., Specific and common genes implicated across major mental disorders: A review of metaanalysis studies, Journal of Psychiatric Research (2014), http://dx.doi.org/10.1016/j.jpsychires.2014.09.014 effects were found for BDNF Val66Met (Kanazawa et al., 2007; Seifuddin et al., 2012), but both studies were in smaller cohorts relative to the confirmed study suggesting the null findings may be due to sample characteristics rather than a lack of genetic effects (Supplementary Table 3). Null conflicting effects were also found for DAOA (Seifuddin et al., 2012) and PDLIM5 (Shi et al., 2008c) in mixed ethnic groups, and for SLC6A4 5-HTTLPR in Caucasian samples (Lotrich and Pollock, 2004), each of these in larger cohorts than the original confirmed studies suggesting these confirmed effects may be small and/or due to false positive variability. 3.4. "
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    Affilia 07/2014; 30(1). DOI:10.1177/0886109914544719 · 0.65 Impact Factor
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